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ciclo: XXXV


Functional neurological disorders are common clinical manifestations in neurological practice, also in pediatric settings, representing an emerging clinical challenge for clinicians. Despite its high frequency and the pervasive impact on patients‘ quality of life, this disorder has long been underestimated and often neglected by specialists, representing often only an exclusion diagnosis. For this reason, FNDs still remain poorly characterized by a clinical point of view and misdiagnosed in pediatrics. Currently a renewed interest has risen about FNDs in the last decades. A new approach for a “rule in diagnosis” of this disorder has been proposed focusing on the presence of positive neurological signs of symptoms’ incongruence and inconsistency. Psychological stressors are considered common risk factors for FNDs, but they are no longer needed for a definitive diagnosis. These just described also represent the diagnostic pillars of Functional Neurological Disorder (also called Conversion Disorder) in the Diagnostic and statistical manual of Mental Disorder – 5th edition (DMS-5). Although FNDs represent the second most frequent diagnosis in outpatients of neurological services and account for 5-20% of pediatric neurological consultations; there are no yet defined diagnostic workups or therapeutic guidelines, mostly for the developmental age. The two most frequent FNDs’ subtypes are Functional Motor Disorders (FMDs) and Non Epileptic Attack Disorders (NEADs) that show similarities in the etiology and the pathophysiology and represent variants of clinical manifestations at the interface between neurology and psychiatry. Notwithstanding, they present distinctive features and neurophysiological studies and neuroimaging can represent valid supportive tools for the diagnosis . The pathophysiology of FNDs includes an overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework and dysfunction of brain networks predisposed to voluntary movement processing. A multidisciplinary treatment, with both physical and psychological therapies, has been recommended by clinical evidence in FNDs This doctoral thesis is divided into two parts. In the first part I have reviewed the state of the art of FNDs (phenomenology, etiological understanding and therapeutic approaches ) both in adults and in pediatrics. Afterwards, the integrated neurological and psychiatric model of diagnostic-therapeutic approach is explained. Together with the FND research group of our Institute, we have built this approach to improve clinical, diagnostic and therapeutic management of these patients, with the interest of contributing to the scientific understanding of this pediatric population, still little studied. The second part is constituted by the experimental work of my thesis based on four prospective and retrospective cohort studies on FNDs pediatric patients. The results of these studies have been published (Gigliotti et al., 2023 in press). The first experimental research was focused on Functional Motor Disorders (FMDs), in a children and adolescent sample, enrolled during a timeframe of 5 years. The aim of this study was to add novel insights into pediatric FMDs, retrospectively describing their clinical manifestations, mainly regarding defined patterns and motor symptoms. Neurocognitive and psychiatric data were analyzed. Finally, in the prospective part of this study, a short-term clinical outcome was reported in a subset of patients, treated by a multidisciplinary approach. The second work reported experimental research aimed to compare neuropsychological and psychopathological profiles of NEADs and FMDs pediatric patients, carried out in order to identify specific vulnerabilities and therapeutic targets linked with these different clinical manifestations. Among the psychiatric evaluation, an in-depth analysis of personality aspects, through Minnesota Multiphasic Personality Inventory for Adolescence (MMPI-A) is also being performed in the NEADs population, as part as a further line of research focused on the studies of the dissociative dimension reported both in FNDs and in adolescents at risk of psychoticism (UHR) Finally, I reported two works that underline possible difficulties in the differential diagnosis of FNDs and possible supportive tools approach in their diagnostic work out In the first case report, the differential diagnosis was supported by Next Generation Sequencing (NGS) analysis, reporting a case of a PRRT2-related paroxysmal dyskinesia, that was long misdiagnosed with FMDs. The second pilot study deals with the controversial issue of a possible supportive role of Suggestive Seizure Induction Techniques in NEADs differential diagnosis with epilepsy with a look at neuropsychiatric profiles vulnerability. These studies expanded the knowledge on FNDs neurological patterns and psychiatric vulnerabilities in the pediatric age. In the last year, FNDs accounted for 5.3% of the hospitalizations in our pediatric neurology ward, configuring the second most frequent diagnosis after epilepsy. We found seizures type slightly more frequent than motor type and a high female prevalence (80%), as known for this disorder. Non motor-symptoms, such as pain, were often present. The presence of specific neurocognitive and psychopathological profiles underlined the neuropsychiatric nature of FNDs, in which discrepancies between the verbal and perceptual abilities were found as well as anxious and depressive clinical symptoms. A multidisciplinary treatment was suggestable, linked with a positive outcome, as shown in our population. This includes psychotherapy and physiotherapy as well as specific psychopharmacological treatments for any psychiatric disorders that arise during the evaluation. The interest in this research area arises both from clinical needs due to the increase of FNDs reported in the last years, mostly during the pandemics, but also by the neuropsychiatric nature of this disorder, representing an interesting interface between neurology and psychiatry. Because of the increasing interest and emerging clinical challenge for FNDs, our Unit in collaboration with the “Besta” Institute of Milan carried on a multicentric study group of FNDs in pediatric age, with the Neurology section of the Italian child and adolescent Neurology and Psychiatry Society (SINPIA). Deepening the knowledge of the disorder in childhood means understanding its mechanisms, causes, risk and protective factors and this would allow the development of increasingly appropriate treatments and the improvement of patients’ quality of life.

Produzione scientifica

11573/1671373 - 2023 - Psychogenic non-epileptic seizures and functional motor disorders in developmental age: A comparison of clinical and psychopathological features
Gigliotti, F.; Di Santo, F.; Cesario, S.; Esposito, D.; Manti, F.; Galosi, S.; Ferrara, M.; Leuzzi, V.; Baglioni, V. - 01a Articolo in rivista
rivista: EPILEPSY & BEHAVIOR ([San Diego, CA] : Elsevier B.V., c2000- San Diego, CA : Academic Press, c2000-) pp. - - issn: 1525-5050 - wos: WOS:000992885000001 (2) - scopus: 2-s2.0-85148345451 (3)

Cesario, Serena; Abbracciavento, Giuseppe; Basile, Consuelo; Gigliotti, Federica; Manti, Filippo; Esposito, Rita Maria; Mastrangelo, Mario - 04d Abstract in atti di convegno
congresso: 14th European Pediatric Neurology Society Congress (Glasgow)
libro: 14th European Paediatric Neurology Society Congress - (978-3-00-072065-9)

11573/1648094 - 2022 - Loss of Continuity of Care in Pediatric Neurology Services during COVID-19 Lockdown: An Additional Stressor for Parents
Cesario, Serena; Basile, Consuelo; Trevisan, Matteo; Gigliotti, Federica; Manti, Filippo; Esposito, Rita Maria; Abbracciavento, Giuseppe; Mastrangelo, Mario - 01a Articolo in rivista
rivista: CHILDREN (Basel: MDPI AG, 2014-) pp. 867- - issn: 2227-9067 - wos: WOS:000816459600001 (2) - scopus: 2-s2.0-85132172020 (3)

11573/1643100 - 2022 - Suggestive Seizure Induction technique in a pediatric PNES population related to neurocognitive and psychological profile: a pilot study.
Cesario, Serena; Esposito, Dario; Gigliotti, Federica; Baglioni, Valentina; Di Santo, Federica; Mastrangelo, Mario - 04d Abstract in atti di convegno
congresso: 14th European Pediatric Neurology Society Congress (Glasgow)
libro: 14th European Paediatric Neurology Society Congress - (978-3-00-072065-9)

11573/1654011 - 2022 - Presenting Patterns of Genetically Determined Developmental Encephalopathies With Epilepsy and Movement Disorders: A Single Tertiary Center Retrospective Cohort Study.
Mastrangelo, M; Galosi, S; Cesario, S; Renzi, A; Campea, L; Leuzzi, V. - 01a Articolo in rivista
rivista: FRONTIERS IN NEUROLOGY (Lausanne: Frontiers Research Foundation, 2010-) pp. - - issn: 1664-2295 - wos: WOS:000820288300001 (3) - scopus: 2-s2.0-85133635447 (3)

Mastrangelo, Mario; Galosi, Serena; Cesario, Serena; Esposito, Rita Maria; Campea, Lucilla; Leuzzi, Vincenzo - 04d Abstract in atti di convegno
congresso: 14th European Pediatric Neurology Society Congress (Glasgow)
libro: 14th European Paediatric Neurology Society Congress - (978-3-00-072065-9)

11573/1614156 - 2021 - Functional neurological disorders in childhood and adolescence: Epidemiology and phenomenology of an emerging diagnostic and clinical challenge
Baglioni, V.; Cesario, S.; Gigliotti, F.; Galosi, S.; Di Maggio, C.; Ferrara, M.; Leuzzi, V.; Di Santo, F. - 01h Abstract in rivista
rivista: EUROPEAN PSYCHIATRY (Editions Scientifique & Medical Elsevier:23 Rue Linois, F 75724 Paris Cedex 15 France:011 33 1 71724646, INTERNET:, Fax: 011 33 1 71724664) pp. S247-S248 - issn: 0924-9338 - wos: WOS:000693667600216 (0) - scopus: (0)

11573/1495255 - 2021 - The relation between sleep and neurocognitive development in infancy and early childhood: A neuroscience perspective
Basile, Consuelo; Gigliotti, Federica; Cesario, Serena; Bruni, Oliviero - 02a Capitolo o Articolo
libro: Advances in Child Development and Behavior - ()

11573/1495248 - 2021 - Co-occurring SYNJ1 and SHANK3 variants in a girl with intellectual disability, early-onset parkinsonism and catatonic episodes
Galosi, S.; Martinelli, S.; Pannone, L.; Terrinoni, A.; Venditti, M.; Pizzi, S.; Ciolfi, A.; Chillemi, G.; Gigliotti, F.; Cesario, S.; Tartaglia, M.; Leuzzi, V. - 01f Lettera, Nota
rivista: PARKINSONISM & RELATED DISORDERS ([S.l.] : Elsevier Science) pp. - - issn: 1873-5126 - wos: WOS:000632026700002 (1) - scopus: 2-s2.0-85099868819 (1)

11573/1509396 - 2021 - Sleep terrors-A parental nightmare
Gigliotti, Federica; Esposito, Dario; Basile, Consuelo; Cesario, Serena; Bruni, Oliviero - 01a Articolo in rivista
rivista: PEDIATRIC PULMONOLOGY ([New York, N.Y.] : Wiley) pp. - - issn: 1099-0496 - wos: WOS:000623483600001 (4) - scopus: 2-s2.0-85101792975 (4)

11573/1473886 - 2019 - A novel developmental encephalopathy with epilepsy and hyperkinetic movement disorders associated with a deletion of the sodium channel gene cluster on chromosome 2q24.3
Mastrangelo, M.; Mei, D.; Cesario, S.; Fioriello, F.; Bernardini, L.; Brinciotti, M.; Guerrini, R.; Leuzzi, V. - 01f Lettera, Nota
rivista: PARKINSONISM & RELATED DISORDERS (Elsevier Science:Molenwarf 1, 1014 AG Amsterdam The Netherlands:011 31 20 4853597, EMAIL:, INTERNET:, Fax: 011 31 20 4853249) pp. 1-3 - issn: 1353-8020 - wos: WOS:000503086600001 (2) - scopus: 2-s2.0-85072683392 (3)

11573/1475651 - 2019 - Update on the treatment of vitamin B6 dependent epilepsies
Mastrangelo, Mario; Cesario, Serena - 01g Articolo di rassegna (Review)
rivista: EXPERT REVIEW OF NEUROTHERAPEUTICS (-London, United Kingdom: Expert Reviews Ltd -London, United Kingdom: Future Drugs Limited) pp. - - issn: 1473-7175 - wos: WOS:000479355400001 (12) - scopus: 2-s2.0-85073182968 (12)

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